Onkológia 4/2013

Role of pathologist in the diagnosis of cancer of unknown primary origin

Metastatic tumors of unknown primary origin (cancer of unknown primary – CUP) account for 3-5% of all malignant tumors. In terms of histogenesis and clinical presentation CUP is a heterogeneous group of tumors, in which adenocarcinomas predominate. The key moment of diagnostic algorithm of CUP is biopsy, with multistep evaluation. At the first level, histogenetic origin of the tumor is established, than followed by its further subtyping, and the third level is designed to obtain information identifying the organ site of the primary tumor. Gold standard in the diagnosis of CUP is immunohistochemical analysis, which is able to detect certain structural cell proteins, e.g. various transcription factors and cell products. Immunohistochemical examination is based on algorithms, building the diagnosis on evidence or absence of expression of selected markers at each level of the algorithm. The most important diagnostic markers are intermediate filaments, for example cytokeratins and vimentin. Using a combination of selected types of cytokeratins, for example CK7 and CK20, it is possible in some cases of CUP to identify the site of the primary tumor. Less frequently are used electron microscopy and cytogenetics, and some benefit can be also obtained by molecular analysis of CUP. Diagnosing CUP is extremely difficult, because it is not only an evaluation of the single tumor entity, but comprises the whole spectrum of histogenetically and biologically diverse malignant tumors with significantly different prognostic and clinical characteristics. Examination of the biopsy is not able to solve this problem alone, and the pathologist becomes dependent on additional clinical information and results from the imaging studies.

Keywords: cancer, carcinoma, metastasis, unknown primary, biopsy, immunohistochemistry.